Identification of Heparan Sulfate in Dilated Cardiomyopathy by Integrated Bioinformatics Analysis

Wenyu Song; Fujian Lu; Zequan Ding; Liqi Huang; Kui Hu; Jinmiao Chen; Lai Wei

doi:10.3389/fcvm.2022.900428

Identification of Heparan Sulfate in Dilated Cardiomyopathy by Integrated Bioinformatics Analysis

Front Cardiovasc Med. 2022 May 27:9:900428. doi: 10.3389/fcvm.2022.900428. eCollection 2022.

Authors

Wenyu Song¹, Fujian Lu², Zequan Ding³, Liqi Huang¹, Kui Hu⁴, Jinmiao Chen¹, Lai Wei¹

Affiliations

¹ Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
² Department of Cardiology, Boston Children's Hospital and Harvard Medical School, Boston, MA, United States.
³ Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, China.
⁴ Department of Cardiovascular Surgery, Guizhou Provincial People's Hospital, Guiyang, China.

Abstract

Objectives: Heparan sulfate (HS) forms heparan sulfate proteoglycans (HSPGs), such as syndecans (SDCs) and glypicans (GPCs), to perform biological processes in the mammals. This study aimed to explore the role of HS in dilated cardiomyopathy (DCM).

Methods: Two high throughput RNA sequencing, two microarrays, and one single-cell RNA sequencing dataset of DCM hearts were downloaded from the Gene Expression Omnibus (GEO) database and integrated for bioinformatics analyses. Differential analysis, pathway enrichment, immunocytes infiltration, subtype identification, and single-cell RNA sequencing analysis were used in this study.

Results: The expression level of most HSPGs was significantly upregulated in DCM and was closely associated with immune activation, cardiac fibrosis, and heart failure. Syndecan2 (SDC2) was highly associated with collagen I and collagen III in cardiac fibroblasts of DCM hearts. HS biosynthetic pathway was activated, while the only enzyme to hydrolyze HS was downregulated. Based on the expression of HSPGs, patients with DCM were classified into three molecular subtypes, i.e., C1, C2, and C3. Cardiac fibrosis and heart failure were more severe in the C1 subtype.

Conclusion: Heparan sulfate is closely associated with immune activation, cardiac fibrosis, and heart failure in DCM. A novel molecular classification of patients with DCM is established based on HSPGs.

Keywords: bioinformatics; cardiac inflammation and fibrosis; dilated cardiomyopathy; heparan sulfate; molecular subtype.